Immunity to malaria has a multicomponent basis which requires the participation of both T- and B-lymphocyte systems. Previous studies have suggested that the T-lymphocyte system has an essential role in 're-infection immunity' to malaria, but that B cells and/or their products are necessary for the host to survive acute infection and to clear the blood of parasites during chronic malaria. Thus, B-cell-deficient mice and chickens died of fulminant malaria when infected with Plasmodium yoelii and Plasmodium gallinaceum, respectively, but when their acute infections were controlled with subcurative chemotherapy, B-cell-deficient host developed chronic low-grade infections and resisted challenge with homologous parasites. In contrast, athymic nude mice failed to control their endogenous P. yoelii infection after the termination of drug therapy unless they had been thymus grafted before initiation of acute infection. We now report that Plasmodium chabaudi adami (556KA) infection in B-cell-deficient mice results in an activation of a T-cell-dependent immune mechanism which terminates acute malaria in a similar way to that seen in immunologically intact mice. Furthermore, these immunized B-cell-deficient mice were resistant to homologous challenge infection as well as infections initiated with Plasmodium vinckei, but not with P. yoelii and Plasmodium berghei.